Alzheimer’s disease destroys memory by degrading neurons that pass signals with the help of the neurotransmitter acetylcholine. Current treatments compensate by increasing acetylcholine levels in the brain, but these drugs offer only modest benefits. They also cause side effects because the extra neurotransmitter activates some classes of acetylcholine receptors that aren’t involved in cognition. Now, researchers at Merck Research Laboratories in West Point, Pa., have identified a compound that selectively boosts the activity of the specific acetylcholine receptor—known as M1—that’s associated with cognition. William J. Ray and colleagues zeroed in on the compound, benzyl quinolone carboxylic acid (BQCA), by screening more than 1 million substances (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0900903106). The researchers showed that this orally active compound improves memory in mice. They also found that BQCA is an allosteric modulator that alters the M1 receptor’s conformation, thereby reducing the amount of acetylcholine necessary to activate it. Allosteric modulation represents a promising therapeutic strategy for Alzheimer’s and other cognitive disorders, Ray notes.